JP2005194215A - Orally ingested substance containing bittern - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide quasi-drugs, pharmaceuticals, luxury foods, groceries and functional foods which are effective for activating salivary immune. <P>SOLUTION: The quasi-drugs, pharmaceuticals, luxury foods, groceries, functional foods, and the like, contain bittern to stimulate lymphatic tissues in salivary gland comprising parotid gland, submaxillary gland, sublingual gland, or the like, induce immune response, markedly increases the number of lymphocytes in the saliva and exerts an enhancing effect on secretory IgA production. <P>COPYRIGHT: (C)2005,JPO&NCIPI

Description

The present invention relates to novel cosmetics, quasi-drugs, pharmaceuticals, luxury goods, miscellaneous goods and functional foods characterized by activation of saliva immunity containing bittern.
The present invention also relates to a method for stimulating salivary immunity by adding an aqueous solution containing 0.1% by weight or more of bittern to oral intake.

  Until now, elucidation of the immune system of the systemic system including the thymus, bone marrow, spleen and peripheral system has been promoted, such as the characteristics of the immunocompetent cells constituting this, the transmission mechanism through cytokines and receptors as communication between cells, etc. Elucidation has been made. The mechanism of action of the systemic immune system that responds when foreign bodies such as pathogens and allergens enter the body has been elucidated, and new vaccines and immunotherapy based on these findings have been developed.

  On the other hand, it has recently been found that a local immune mechanism different from the conventional systemic immune mechanism exists in the exocrine organs such as the digestive system, respiratory system and urogenital system. It is also called the mucosal immune system.

The human body is in contact with the outside world through the skin covering the body surface and the local mucous membrane. Unless the pathogen enters through trauma or blood-sucking insects, the skin and mucous membrane are the first invaders of the pathogen. The surface of the skin is dry and consists of several layers of cells, making it difficult for pathogens to enter. However, the mucous membrane covering the entrance portion of the body lumen, especially the intestinal mucosa, is always moist for digestion and absorption of food, and is an environment suitable for bacterial invasion and survival.
In particular, the oral cavity is the entrance to the digestive system and is directly exposed to foreign antigens. The surface of the intestinal tract including the oral cavity is covered with a thick sticky mucus layer, and this adhesiveness acts as a physical and chemical barrier when a pathogen enters the oral cavity. It is well known that the main role is played by an immunoglobulin called IgA. The mucus component exhibiting viscosity is composed of mucin, lysozyme, peroxidase, lactoferrin, histatin and the like in addition to secretory IgA. Each of these immune systems is an innate immune system that each person has, and is considered to be a non-specific defense barrier that does not specify an antigen.

On the other hand, there is naturally a secretory IgA as an antigen-specific barrier that identifies the antigen.
These functions of the immune system include blocking adhesion of pathogenic microorganisms to the mucosal epithelium and enamel, neutralizing pathogenic bacterial toxins, neutralizing viruses, and various antigen aggregation activities.
The production of secretory IgA is strongly induced by antigen stimulation, and the production of secretory IgA in the local mucosa in the oral cavity is thought to be brought about by B cells that have migrated. The secretory IgA production mechanism in the salivary glands will be described in a little more detail.

  The induction and production of secretory IgA in the saliva of the oral cavity in the exocrine gland is called the circulation homing pathway. The invading antigen through the oral cavity and nostril is first taken up by M cells present in Peyer's patches in the intestine, and then presented as macrophages and dendritic cells under the epithelial cells covering Peyer's patches. The information is provided to T lymphocytes via the cells. T lymphocytes stimulate IgA-producing progenitor B cells that are frequently present in this tissue and produce various cytokines. Activated IgA-producing progenitor B cells are differentiated, leave the Peyer's patch, pass through the intestinal lymph nodes, enter the systemic circulation via the thoracic duct, and migrate to peripheral blood. The B lymphocytes on the peripheral blood selectively reach the salivary glands and the lamina propria which are the execution tissues. This is called circulation homing. When this circulating homogeneous B lymphocyte is subjected to antigen stimulation again, it is differentiated into plasma cells by the action of cytokines produced by T cells, and an antibody specific to the antigen in the salivary gland, that is, an antibody called secretory IgA It is thought to induce.

It has been elucidated that this mucosal immune system operates based on induction and control mechanisms different from those of the thymus, bone marrow systemic system and peripheral immune system which have been elucidated so far.
As an example of its application, many vaccines have been developed and we have escaped the disease by antigen administration by injection, which is a commonly used method. Thus, it is certain that an antigen-specific immune response is effectively induced against the systemic immune system. However, a simple method using activation of the mucosal immune system for the prevention of diseases such as respiratory system, digestive system and oral medicine has not yet been found.
Hoshin Hoshin: Strategies for prevention of infection with solid pathogens by salivary IgA, dentistry report, vol. 99, No, 11, 965-971, '99

Therefore, the present inventors have reasoned that there is a thing that promotes the secretion stimulation of salivary antibodies in foods that people usually eat.
We thought that it is possible to induce an immune response and prevent disease through the local mucosal system by eating and drinking a substance that functions as an antigen. .
The present invention aims to stimulate salivary immunity by inducing lymphocytes and secretory IgA antibodies in the peripheral lymph glands by stimulating the salivary glands of the oral cavity corresponding to the entrance of the intestinal tract.
As a result, the effect of the salt contained in bittern was recognized and the present invention was achieved.
And it aims at providing the oral ingestion which has the effect of stimulating salivary immunity by applying these active ingredients.

The oral cavity is an important organ that supports the human's intellectual activities such as vocalization and conversation, as well as the original life activities such as eating, digestion, and breathing. Saliva is indispensable for maintaining the function of the oral cavity. . The oral cavity is the entrance to the digestive tract such as the stomach, duodenum, small intestine, and large intestine. It can be said that it is part of the intestinal tract.
Saliva is secreted into the oral cavity mainly from the parotid gland, the submandibular gland, the large salivary gland of the sublingual gland, and a large number of small salivary glands to form mixed saliva. The function of saliva includes cleaning, antibacterial protection of teeth and oral mucosa, in addition to physiological functions such as wetting, smoothing, digestion and pronunciation and taste.
The immune system against infection acts on the mucous membrane, mainly the digestive tract. The oral cavity is also a part of the digestive tract, and it is covered with a tissue with a developed immune mechanism called a mucosa-related lymphoid tissue.

The main role of oral mucosal immunity, ie salivary immunity, is secretory IgA. This antibody aggregates foreign substances, neutralizes and inactivates toxins produced by viruses and pathogenic bacteria, It has an antibacterial effect by preventing adhesion and has a function of preventing infection.
The bittern-containing oral intake in the present invention is a temporarily acting pseudoantigen, and the sensitized portion as the antigen is the salivary gland in the oral cavity, resulting in stimulation of mucosal immunity, and the lymphocytes in the mixed saliva Activation of salivary immunity is achieved by increasing and enhancing production of secretory IgA, and the present invention utilizes this effect.
The bittern used in the present invention is composed mainly of magnesium chloride, and is composed of magnesium sulfate, calcium sulfate, potassium chloride and sodium chloride, and further contains trace amounts of iron, zinc, copper, iodine, phosphorus, selenium and manganese. contains. In the practice of the present invention, the shape of the bittern may be crystalline or liquid. In addition, the bittern in the present invention uses an anhydrous conversion value.

The basic configuration of the present invention is as follows.
(1) A bittern-containing oral intake characterized by activation of salivary immunity comprising an aqueous solution containing 0.1% by weight or more of bittern.
(2) The oral intake according to (1), characterized by stimulating salivary immunity comprising magnesium, calcium, sodium, potassium, and counter ions of chlorine and sulfate, which are main components when bittern dissociates in an aqueous solution.
(3) The oral intake according to (1) or (2), wherein the activation of salivary immunity enhances the increase of lymphocytes in the oral cavity and / or the production of secretory immunoglobulin IgA.
(4) The oral intake according to any one of (1) to (3), wherein the oral intake is a quasi drug, a pharmaceutical product, a luxury product, a miscellaneous goods, and a functional food.
(5) A method for improving the activation of saliva immunity in an oral intake, wherein the saliva immunity is activated by adding an aqueous solution containing 0.1% by weight or more of bittern to the oral intake.
(6) The method for improving the salivary immunity activation of the oral intake according to (5), wherein the oral intake is a quasi-drug, a pharmaceutical product, a luxury product, a miscellaneous goods, and a functional food.

In the present invention, quasi-drugs, pharmaceuticals, miscellaneous goods include brushing agents, mouthwashes, gargles, luxury products include gums, candy, functional foods such as bittern sheets.
In the present invention, it is necessary that the oral intake for stimulating salivary immunity contains an aqueous solution containing 0.1% or more, preferably 0.2% or more of bittern. Although there is no restriction | limiting in the upper limit of the bittern content in aqueous solution, For example, in the aqueous solution 10% or more, it has confirmed that the sustained effect of the increase in lymphocytes was prolonged.

The present inventors newly stimulated the salivary gland lymph tissue consisting of parotid gland, submandibular gland, sublingual gland, etc. in the oral cavity in the local mucosal immune system, and induced an immune response in the saliva. The present inventors have found an effect that causes a marked increase in lymphocytes and an increase in production of secretory IgA.
The bittern can be used alone or in combination with other materials for functional foods, quasi drugs, pharmaceuticals, luxury goods, miscellaneous goods and the like.
Applying the present invention, bittern-containing oral intake characterized by the activation of salivary immunity is very simple for the prevention of people's diseases, especially for respiratory, digestive and oral medicine diseases. It can be used as a thing.

On a daily basis, many foods, food additives, luxury goods, beverages, etc. to be consumed were actually eaten, and mixed saliva was collected and used for measurement. For example, for foods that are soluble in water, rinse the mouth with distilled water once before eating the test substance, collect saliva as a control, and then keep the test substance in the mouth for 1 minute before expelling After the mouth was washed again with distilled water, saliva was collected and used for measurement immediately and after 30, 60, 90, and 120 minutes had elapsed for a certain period of time.
All tests were conducted in the morning to avoid diurnal variation.
The number of lymphocytes was counted using a hemocytometer (HIRSCMANN LABORGERATE) attached to a microscope (Olympus).
The lymphocytes in the saliva before washing the oral cavity may contain some neutrophils having granules derived from the gingival crevicular fluid, but they are removed by washing before the test. Therefore, the leukocytes actually counted can be considered as lymphocytes derived from the salivary gland and lymph gland.
In the case where the number of lymphocytes increased from the number of controls before ingesting the test substance, it was partially subjected to measurement of secretory IgA. An ELISA (enzyme-linked immunosorbent assay) method that specifically detects secretory IgA was used as the quantification method.

  An aqueous solution containing 0.2%, 1.0, 5.0, and 10.0% bittern was prepared and used as a test object. In all five of the five subjects, the number of lymphocytes increased 1.5 to 4.0 times compared to the control after 60 and 90 minutes, and began to decrease after 120 minutes.

  An aqueous solution containing 0.2%, 1.0% and 5.0% sodium chloride containing 5% bittern was prepared and used as a test object. In all the test subjects, the number of lymphocytes increased by 1.5 to 3.0 times after 60 and 90 minutes compared to the control in 4 of 5 subjects, and turned to decrease after 120 to 150 minutes. One person has hardly changed.

An aqueous solution containing 1.0 and 5.0% of magnesium chloride (hexahydrate), magnesium sulfate (7-hydrate) and sodium chloride, respectively, as reagents was prepared and used as a test object.
In the test subjects of magnesium chloride and magnesium sulfate, all of the five subjects had five to five lymphocytes, and the number of lymphocytes increased 1.5 to 3.0 times compared to the control after 60 and 90 minutes. In all cases, the number of lymphocytes in 4 out of 5 subjects increased 1.5 to 2.5 times compared to the control after 60, 90 minutes, and all decreased after 120 minutes.

(Comparative Example 1)
An aqueous solution containing 1.0% each of potassium chloride and calcium chloride (dihydrate) as reagents was prepared and used as a test object.
In all of the test subjects, there was a slight increase in lymphocytes in 3 out of 3 subjects.

(Application example of dentifrice)
As a component of a dentifrice, a commonly used basic composition is 54% calcium carbonate as an abrasive, 34.8% sorbit as a lubricant, 5.0% glycerin, 1.0% carrageenan as a thickener, A blank consisting of 4.7% foaming agent and 0.5% mint oil as a refreshing agent is used as a blank. Add bittern and salt to this basic formulation and add 15% by internal percentage. The ratio of bittern and salt was adjusted to 2/1 (bitum toothpaste A), 1/1 (same C), and 1/2 (same B).
A test of salivary immunity was carried out using 10 test subjects and the previously prepared dentifrice test article.
Saliva was collected before, after brushing, and after 30, 60, 90, and 120 minutes. Before the collection, the mouth was rinsed with distilled water.
The results of changes in the number of lymphocytes and production of secretory IgA are shown in FIGS. 1 and 2 with the value before brushing being 100.

The number of lymphocytes is 2/1 (A), 1/1 (C), 1/2
In any of the dentifrices of (B), a significant increase was observed after 90 minutes of brushing, compared to before brushing. The amount of change was small in the blank dentifrice.
Secretory IgA is determined in the subject (A) compared to before brushing 30, 60
, After 90 minutes, a significant increase is observed, which increases with other subjects (B), (C)
It was big compared with. In the test substance (B), a significant increase was observed after 30, 90 minutes.
In the blank dentifrice of the basic formulation, the production amount of secretory IgA remained almost unchanged after 30, 60, 90, 120 minutes from immediately after brushing, and there was no tendency to stimulate the immune system.

(Application example of bitterness-containing luxury products)
A long sheet mainly composed of soluble starch containing 10% bittern was prepared by a casting method, and used as a strip-shaped test article having a width of 2.0, a length of 5.0 cm and a thickness of 0.1 mm.
Three subjects were used.
After washing the mouth, saliva is collected as a control, and when a test substance is subsequently placed in the mouth, it dissolves quickly. Two minutes later, the mouth was washed, and immediately after 30, 60, 90 and 120 minutes, saliva was collected. Three out of three individuals increased the number of lymphocytes by 2.0 to 3.0 times after 60 and 90 minutes compared to the control. After 120 to 150 minutes, a decreasing tendency was shown.

(Application example of bittern-containing drinking water)
Drinking water (trade name “Tenkai no Mizu”, Ako Kasei Co., Ltd.) adjusted to a hardness of 1000 using bittern obtained from deep ocean water was used as the test object. There were 8 subjects.
After washing the mouth, saliva was collected as a control, followed by rinsing the mouth with a test substance for 30 seconds and drinking. Immediately thereafter, saliva was collected after 30, 60, 90 and 120 minutes.
Seven out of eight people showed a marked increase of 1.5 to 3.0 times the number of lymphocytes after 60 and 90 minutes compared to the control, and saturated or slightly decreased to a constant value after 120 minutes. Showed a trend.

Change in the number of lymphocytes over time Time course of secretory IgA production

Claims (6)

A bittern-containing oral intake characterized by stimulating salivary immunity comprising an aqueous solution containing 0.1% by weight or more of bittern. The oral ingestion according to claim 1, characterized by stimulating salivary immunity consisting of magnesium, calcium, sodium, potassium, and counter ions of chlorine and sulfate, which are main components when bittern dissociates in an aqueous solution. The oral intake according to claim 1 or 2, wherein the activation of salivary immunity enhances both or both of the increase of lymphocytes in the oral cavity and the production of secretory immunoglobulin IgA. The oral intake according to any one of claims 1 to 3, wherein the oral intake is a quasi-drug, a pharmaceutical, a luxury product, a miscellaneous goods, and a functional food. A method for improving the activation of saliva immunity in an oral intake, wherein the saliva immunity is activated by adding an aqueous solution containing 0.1% by weight or more of bittern to the oral intake. 6. The method for improving the activation of salivary immunity of an oral intake according to claim 5, wherein the oral intake is a quasi-drug, a pharmaceutical product, a luxury product, a miscellaneous product, and a functional food.